Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome.

Publication Type:

Journal Article

Authors:

Matsuo, Yoshiyuki; Tanaka, Masashi; Yamakage, Hajime; Sasaki, Yousuke; Muranaka, Kazuya; Hata, Hiroaki; Ikai, Iwao; Shimatsu, Akira; Inoue, Mayumi; Chun, Tae-Hwa; Satoh-Asahara, Noriko

Source:

Metabolism, Volume 64, Issue 11, p.1490-9 (2015)

Keywords:

Aged, Biomarkers, Female, Humans, Intra-Abdominal Fat, Male, Metabolic Syndrome, Middle Aged, Obesity, Postmenopause, Premenopause, RNA, Messenger, Thrombospondin 1, Weight Loss

Abstract:

<p><b>CONTEXT: </b>Thrombospondin 1 (THBS1 or TSP-1) is an adipose-derived matricellular protein, which has recently been highlighted as a potential mediator of insulin resistance and adipose inflammation in obesity.</p><p><b>OBJECTIVE: </b>In this study, we aimed to determine the clinical significance of THBS1 as a novel biological marker of visceral obesity, metabolic syndrome, and diabetes.</p><p><b>METHODS: </b>The THBS1 mRNA level was quantified with real-time PCR in human adipose tissues obtained from 16 non-obese subjects. The relationships between serum THBS1 level and obesity/diabetes traits as well as the diagnostic components of metabolic syndrome were assessed in 164 normal-weight or overweight/obese subjects (78 males and 86 females; mean age, 50.4; mean BMI, 29.8) with analysis of covariance (ANCOVA) and regression analyses.</p><p><b>RESULTS: </b>THBS1 was predominantly expressed in visceral adipose tissues relative to subcutaneous adipose tissues (P<0.001). The visceral THBS1 expression was positively associated with the body mass index (BMI; γs=0.54, P=0.033). ANCOVA demonstrated that the THBS1 level is associated with abdominal obesity (P<0.001), hyperglycemia (P=0.02), and hypertension (P=0.04). Multivariable regression analysis suggested an association between serum THBS1 and fasting plasma glucose levels. The associations between serum THBS1 levels and obesity/diabetes traits were found preferentially in women (BMI, γs=0.30, P=0.05; FPG, γs=0.26, P=0.016). Subanalyses demonstrated that the association with obesity traits was predominantly found in premenopausal women (BMI, γs=0.41, P=0.007), whereas the association with diabetes traits was predominant in postmenopausal women (HbA1c, γs=0.38, P=0.01). During medical weight reduction treatment, the change in the serum THBS1 level was associated with the change in BMI and HbA1c in pre- and postmenopausal women, respectively.</p><p><b>CONCLUSIONS: </b>Serum THBS1 is a useful biological marker of obesity and metabolic syndrome in Japanese subjects, particularly in women. THBS1 may act as a critical circulating factor that couples obesity with metabolic syndrome and diabetes in humans.</p>